Transformation produces many changes in cell physiology. To study these changes, we developed two new techniques: 1) a new procedure for electron microscopic localization of labelled antibodies with good morphologic preservation (EGS procedure) and 2) a new technique using intensifier target video cameras to observe the fate of small numbers of fluorescently labeled molecules or high magnification light microscopic detail in living cells. With these new tools, we have studied receptor-mediated endocytosis, using the uptake of alpha-macroglobulin (alpha 2 M) as an example. We have found that hormones such as insulin and EGF (epidermal growth factor) are internalized by receptor-mediated uptake in the same vesicles as alpha 2M. These vesicles move about in the cytoplasm by saltatory motion and do not immediately fuse with lysosomes. By electron microscopy, these vesicles are the "coated" class of endocytic vesicles and by antibody localization, alpha 2M reaches the lysosomal population after many hours.